Isolation and characterization of glycosaminoglycans in human brain of different age groups.

Five distinct glycosaminoglycan fractions have been isolated from human brain of various age groups, by employing an improved fractionation procedure. Analysis of these fractions showed that human brain contains hyaluronic acid, chondroitin-4sulphate, chondroitin-6-sulphate, dermatan sulphate, heparan sulphate and two unidentified low sulphated fractions. The pattern of variation of these compounds with age, indicates that they may be playing an important role in the process of myelination and brain maturation. STUDIES from several laboratories have established the presence of glycosaminoglycans (GAG) in the tissues of the central nervous system. But two important points still remain to be established: (i) the exact nature of GAG and (ii) the physiological role of these compounds in brain. There is general agreement on the occurrence of hyaluronic acid and chondroitin sulphates in the brain; but a complete characterization of these compounds has yet to be achieved. SZABO and ROBOZ-EINSTEIN (1962) isolated hyaluronic acid and chondroitin-4-sulphate from bovine brain, while CLAUSEN and HANSEN (1 963) demonstrated the presence of hyaluronic acid, dermatan sulphate and chondroitin-6sulphate in human brain. On the other hand, MEYER, HOFFMAN, GRUMBACH and SAMPSON (1959) reported the presence of dermatan sulphate and heparan sulphate in the brain of a gargoyle patient; and hyaluronic acid and heparan sulphate in the brain of a child used as the normal control in this study. Earlier work from this laboratory on GAG of sheep brain (SINGH and BACHHAWAT, 1965) showed the presence of some minor components of GAG fractions, not fully characterized, along with hyaluronic acid, chondroitin-6-sulphate and chondroitin-4-sulphate. In the present investigation, an attempt has been made to get a profile of uronic acid-containing GAG in human brain, of various age groups, as completely as possible, employing improved techniques of isolation. Although the postulation of BRANTE (1958), as to the possible role of these compounds in the process of myelination has attracted the attention of many workers in this field, very little is known regarding the functional aspect. Earlier work from this laboratory (GUHA, NORTHOVER and BACHHAWAT, 1960; BALASUBRAMANIAN and BACHHAWAT, 1964; SINGH and BACHHAWAT, 1965) provided evidence of the importance of these compounds in the processes of myelination and brain maturation. Work of SZABO and ROBOZ-EINSTEIN (1962) also indicated that hyaluronic acid may be one of the building blocks of the myelin sheath. Abbreviations used: GAG, glycosaminoglycans; CPB, cetyl pyridinium bromide.